update on iso activities -...

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Update on ISO activities

Lutz Grohmann, Marco Marzarra, Hermann Broll

3rd International Workshop on Harmonisation of GMO Detection and Analysis for Central and South America, Cartagena, Colombia,

3 - 4 July 2012

Harmonisation of GMO Detection and Analysis for Central and South America, Cartagena, Colombia, 3 - 4 July 2012

International Organization for Standardization (ISO)

The International Organization for Standardization widely known as ISO, is an international-standard- setting body composed of representatives from various national standards organizations;

ISO is a non-governmental organization;

It is setting standards that often become law, either through treaties or national standards;

Therefore it makes it more powerful than most non-governmental organizations.

Standards, technical specifications etc are usually developed together with experts from governmental organisations, company representatives and other interested stakeholders.


PASC EASC

PASC

ACCSQ

PASC

ARSO

AIDMO

CEN EASCEASC

COPANT

PASCPASC

COPANT

CEN

AIDMO

ARSO

EASC

PASC PASC

PASC

MO/LDE9606B.CDR2003-03-19

CCSQCCSQACCSQ

Regional standardization bodies

European Committee for Standardization

Euro-Asian Council for Standardization, Metrology

and Certification

Asean Consultative

Committee for Standards and Quality

Arab Industrial Develop-

ment and

Mining Organi-

zation

African Regional Organization for Standardization

Pan American Standards Commission

Pacific Area Standards Congress


CEN TC 275 Food analysis - Horizontal methods WG 11: Genetically modified foodstuffs Convener: Dr. Marianna Schauzu, Federal Institute for Risk Assessment, Berlin Secretary: Carola Seiler, DIN, Germany

EN ISO Topic Stage Details

21572

Foodstuffs - Methods for the detection ofgenetically modified organisms and derivedproducts -Protein based method

Standard ratified in November2003

Corrigendum to change the status of the Annexfrom "normative” into “informative” has beenpublished by ISO and is under way in CMC

21571

Foodstuffs - Methods of analysis for thedetection of genetically modified organismsand derived products -Nucleic acid extraction

Standard ratified in February2005

21569

Foodstuffs - Methods of analysis for thedetection of genetically modified organismsand derived products -Qualitative nucleic acid based methods

Standard ratified in June 2005

24276

Foodstuffs - Nucleic acid based methods ofanalysis for the detection of geneticallymodified organisms and derived products -General requirements and definitions

Standard ratified in January2006

21570

Foodstuffs - Methods of analysis for thedetection of genetically modified organismsand derived products -Quantitative nucleic acid based methods

Standard ratified in October2005

21568Foodstuffs - Methods of analysis for thedetection of genetically modified organismsand derived products – Sampling

European Technical Standard2006 No agreement within ISO


Sampling CEN/TS 15568 consignment lab sample

General docum

ent ENISO

24276

Protein based methods EN ISO 21572

Extractiontest sample Protein

GMO detectionProtein test result

Screening

Identification

Quantitation

DNA based methods

GMO detectionDNA test result

ScreeningEN ISO 21569 Qualitative PCR

IdentificationEN ISO 21569 Qualitative PCR

QuantitationEN ISO 21570 Quantitative PCR

Extraction EN ISO 21571 test sample DNA


2008“According to the Vienna Agreement, the secretariat for the future work on those EN/ISO standards concerning GMO, which were elaborated under CEN/TC 275/WG 11 (CEN-Lead), has been transferred to ISO. The responsible expert group is ISO/TC 34/SC 16 which had its first meeting in Chicago from 11th to 13th November 2008.”

CEN ISO

ISO/TC 034/SC 16 "Horizontal methods for molecular biomarker analysis"


Chairmanship: USDA Secretariat: AOCS


ISO technical committees Σ=269


Scope and composition of SC16

Scope: Horizontal methods for molecular biomarker analysis

Standardization of biomolecular testing methods applied to: foods; feeds; seeds and other propagules of food and feed crops. The scope includes methods that analyze nucleic acids [e.g., polymerase chain reaction (PCR), genotypic analysis and sequencing], proteins [e.g. enzyme linked immunosorbent assay (ELISA)], and other suitable methods. The scope also includes variety identification and detection of plant pathogens. The scope does not include food microbiological methods.


Standards under development

ISO/CD 13484: General requirements for molecular biology using analysis for detection and identification of pathogenic and destructive organisms of the plants and derived products.

ISO/CD 13495: Principles of selection and criteria of validation for the varietal identification methods using specific nucleic acid analysis.

ISO/WD 16383 on Qualitative methods (performance criteria)

ISO 16578 on the use of microarray detection of specific nucleic acid sequences

ISO 16577 Terms and Definitions


Summary of meeting resolutions

Res. 44/11

The Committee debated the classification of documents ..and agreed that reclassification or confirmation of current classification will be decided on a case-by- case basis, especially for TS

Flax FP967 method NWIP was accepted as TS, CD draft now, few comments, will be quickly adopted as standard method

Meetings every 18 months; Next meeting will be in Europe in spring 2013 most probably in London!!


Actual projects on ISO


What is Codex Alimentarius?

Codex Alimentarius (Latin for "food book") is a collection of internationally recognized standards, codes of practice, guidelines and other recommendations relating to foods, food production and food safety;

Codex Alimentarius was established in 1963 by the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO);

In 2006, 99 % of the world’s population were represented in Codex Alimentarius Commission through 174 member countries and one Member Organization (European Union);

Commission's main aims are stated as being to protect the health of consumers and ensure fair practices in the international food trade;

The Codex Alimentarius is recognized by the World Trade Organization (WTO) as an international reference point for the resolution of disputes concerning food safety and consumer protection;

Codex Alimentarius covers all foods, whether processed, semi-processed or raw, but far more attention has been given to foods that are marketed directly to consumers;

It contains general standards covering matters such as food labeling, food hygiene, food additives and pesticide residues, and procedures for assessing the safety of foods derived from modern biotechnology;

It also contains guidelines for the management of official (i.e., governmental) import and export inspection and certification systems for foods;

The Codex Alimentarius is published in Arabic, Chinese, English, French and Spanish.


Codex Alimentarius – scientific sounds

� “The food standards, guidelines and other recommendations of the Codex Alimentarius shall be based on the principle of sound scientific analysis …”;

� Codex Alimentarius work is dedicated to member countries;

� However, since its beginning, the Commission has welcomed the participation of consumers, whose organizations have been represented at its sessions;

� Decisions are made based on consensus; there is normally no voting procedure established;

� Member countries are encouraged to adopted Codex standards, guidelines etc in national regulations.


World Trade Organization (WTO)WTO is an organization that intends to supervise and liberalize international trade.Existing since 1995 (before GATT)The organization deals with regulation of trade between participating countriesThe WTO has 153 members, representing more than 97% of total world tradeDecision making process is generally by consensus, and relative market size is the primary source of bargaining power

Codex Alimentarius is quoted in trade agreements

wikipedia


Relevance of Codex Alimentarius – Fostering consumer protection worldwide

In 1985 United Nations General Assembly Guidelines for consumer protectionStated that:“When formulating national policies and plans with regard to food, Governments should take into account the need of all consumers for food security and should support and, as far as possible, adopt standards from the Food and Agriculture Organization’s ... and the World Health Organization’s Codex Alimentarius ...”.

In 1995 Agreement on the Application of Sanitary and Phytosanitary Measures (SPSS) and Agreement on Technical Barriers to Trade (TBT) of the World Trade Organization (WTO).Formally recognized:International standards, guidelines and recommendations, including the Codex Alimentarius, as reference points for facilitating international trade and resolving trade disputes in international law.


SPS Agreement: Agreement on the Application of Sanitary and Phytosanitary Measures

Article 2.2 of the SPS Agreement states:“Members shall ensure that any sanitary and phytosanitary measure is applied only to the extent necessary to protect human, animal or plant life or health, is based on scientific principles and is not maintained without sufficient scientific evidence ...”.

“The SPS Agreement has identified and chosen the standards, guidelines and recommendations established by the Codex Alimentarius Commission for food additives, veterinary drug and pesticide residues, contaminants, methods of analysis and sampling, and codes and guidelines of hygienic practice. This means that Codex standards are considered scientifically justified and are accepted as the benchmarks against which national measures and regulations are evaluated.”

Codex Alimentarius is quoted in trade agreements (WTO)


TBT Agreement: Agreement on Technical Barriers to Trade It exists to ensure that technical regulations, standards, testing, and

certification procedures do not create unnecessary obstacles to trade;The TBT agreement strongly encourages countries to recognize the results of

other countries' conformity assessment tests – the tests that determine whether a product conforms to a given standard;It also promotes the development of international standards and provides

governments and inter-governmental bodies with guidance on how to best develop such standards. TBT members are strongly encouraged to adopt international standards as their technical requirements whenever possible.

Article 2.6 of the TBT Agreement states:“With a view to harmonizing technical regulations on as wide a basis as

possible, Members shall play a full part, within the limits of their resources, in the preparation by appropriate international standardizing bodies of international standards for products for which they have either adopted, or expect to adopt, technical regulations.”

Codex Alimentarius is quoted in trade agreements (WTO)


Codex Alimentarius is quoted in trade agreements

Codex and its work have been quoted in many bilateral and multilateral trade agreements, including:

Mexico–Bolivia, 1995

Baltic Area Free Trade Agreement, 1996

Chile–Mexico, 1997

Bulgaria–Turkey, 1998

Central America–Chile, 1999

Association of Southeast Asian Nations (ASEAN), 2000

Turkey–Bosnia and Herzegovina, 2002

Australia–Thailand, 2005

United States of America–Australia, 2005


Criteria are applicable to protein and DNA-based methods;

Criteria approach, it is foreseen not to endorse individual methods;

Scope includes applications such as ‘food derived from modern biotechnology’, food authentication, food speciation and other purposes;

Contains the reference to ‘food derived from modern biotechnology’ twice;

Title was modified to reflect the scope; ‘foods derived from modern biotechnology’ is still in the footnote to the title;

Text was modified extensively during the sessions, however major parts are derived from the ENGL document ‘Definition of minimum performance requirements for analytical methods of GMO testing’;

Modular Approach to Method Validation is included;

On several places thresholds are indicated.

PROPOSED DRAFT GUIDELINES ON PERFORMANCE CRITERIA AND VALIDATION OF METHODS FOR DETECTION, IDENTIFICATION AND

QUANTIFICATION OF SPECIFIC DNA SEQUENCES AND SPECIFIC PROTEINS IN FOODS*


Requirements with defined thresholds in the document I:

Repeatability standard deviation (RSDr)21. The relative repeatability standard deviation for the PCR step should be ≤25% over the whole dynamic range of the method.

Reproducibility standard deviation (RSDR)22. The relative reproducibility standard deviation for the PCR step should be below 35% over the majority of the dynamic range, except at the limit of quantification, where the RSDR could be higher.

Robustness23. Robustness is a measure of the capacity of an analytical procedure to remain unaffected by small but deliberate variations in method parameters and provides an indication of its reliability during normal usage. Examples of such variations include: reaction volumes (e.g., 29 vs. 30μl), annealing temperature (e.g., +/- 1oC) and/or other relevant variations. The experiments need to be performed at least in triplicate. The response of an assay with respect to these small changes should not deviate more than ±35% in reproducibility experiments from the response obtained under the original conditions.




Requirements with defined thresholds in the document II:

Sensitivity25. For a quantitative PCR method, a linear relationship of the Ct as a function of the logarithm of the template concentration should be obtained across the range of the method. The correlation coefficient, y-intercept and slope of the regression line should be reported. The % of residual for each of the calibrators should preferably be ≤30%.

30. For assays selective for the target DNA. Experimental evidence of selectivity for the target DNA should include:Two replicates should be analyzed for each DNA sample, which shall give results within a Ct-value of 0.5.

32. For assays on taxon-specific DNA sequences. Experimental evidence of taxon selectivity should include:Two replicates should be analyzed for each DNA sample, which shall give results within a Ct-value of 0.5.

Trueness35. A trueness value of ± 25%, in regards to the PCR step, should be acceptable over the whole dynamic range.




Codex Alimentarius JOINT FAO/WHO FOOD STANDARDS PROGRAMME

http://www.codexalimentarius.net/download/report/738/al33_23e.pdf


Codex Committee for Food Labelling (CCFL)

• In 1999 a WG was established to draft a text regarding GMO labelling• WG comprised Japan, Thailand, India, Brazil, USA, Canada, European

Community• Text was drafted «Proposed draft recommendations for the Labelling of

Food and Food Ingredients derived from Biotechnology»• Options were given for method of production labelling as well as labelling

only for significant changes in composition incl. nutrition

Detection methods were mentioned for the first time in Codex system

Developments within Codex Alimentarius regarding genetically modified foods


Codex Committee for Food Labeling (CCFL)Proposed draft Recommendations for the labelling of foods and food ingredients obtained through certain techniques of genetic modification/genetic engineering (at Step 3)

From „Mandatory Labelling Provisions“

From „Voluntary Labelling Provisions “

There is still no consensus reached; consequently no global standard for gm food labelling is existing

Developments within Codex Alimentarius regarding genetically modified foods


At step 6 of the Codex procedureTo be included as an Annex to the Guidelines on Measurement Uncertainty (CAC/GL 54-2004)

Explanatory Notes to the Codex Guidelines on Measurement Uncertainty

Users of validation data should note that sources of uncertainty that are not covered by validation studies include:- Sampling- Pre-treatment- Method bias- Variation in conditions-Changes in sample matrix

4 different scenarios are described in the guideline (above maximum level incl. MU up to incl. MU less than maximum level)

Useful References

Draft Revised Guidelines on Measurement Uncertainty

Developments within Codex Alimentarius also dedicated to genetically modified foods


1. SCOPE These guidelines provide guidance to governments on the procedures to resolve disputes which arise between food control authorities about the status of a food consignment, when the assessment based on test results made in the importing country disagrees with the assessment made by the exporting country on the same lot. These guidelines only address disputes related to methods of analysis or laboratory performance and do not address questions of sampling. The procedure examines only the validity of the importing country’s results on which non-compliance is alleged. It is recognised that disputes may arise from other cause(s), which should also be investigated.

These guidelines do not cover microbiological test results!

Developments within Codex Alimentarius also dedicated to genetically modified foods GUIDELINES FOR SETTLING DISPUTES OVER ANALYTICAL (TEST) RESULTS (CAC/GL 70-2009)


PREREQUISITES/ASSUMPTIONS for a applying these guidelines are:

•both countries agree on using this guideline;•laboratories comply with quality assurance provisions; •at least one representative sample5 from the same food lot has been taken;•laboratories report quantitative analytical results in the form of “a ± 2u” or “a ± U”•laboratories use specific methods of analysis, which have been endorsed by the Codex Alimentarius

THE RESULTS AND PROCEDURES OF THE LABORATORY OF THE EXPORTING COUNTRY AND ITS COUNTERPART IN THE IMPORTING COUNTRY ARE COMPARED

ANALYSING RESERVE SAMPLE

ANALYSIS OF REMAINING RESERVE SAMPLE by third party (importing country can select a laboratory

The Commission adopted the Draft Guidelines in Thirty-Second Session in 2009

Developments within Codex Alimentarius also dedicated to genetically modified foods GUIDELINES FOR SETTLING DISPUTES OVER ANALYTICAL (TEST) RESULTS (CAC/GL 70-2009)

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Hermann Broll

Department of Food SafetyBundesinstitut für Risikobewertung Max-Dohrn-Str. 8-10

D-10589 Berlin

Tel. 030-18412-0 Fax 030-8412-4741

[email protected] www.bfr.bund.de

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